Abstract:
Background: VACTERAL association involves anal atresia, cardiac defects, renal anomalies,
and limb abnormalities. The aim of our study was to identify the genetic causes of this disorder
in a Palestinian family affected with similar phenotype which could also be a new syndrome.
Methods: Blood samples were collected from five members of a family with VACTERAL
association and then DNA was extracted and subjected to Polymerase Chain Reaction (PCR)
for suspected genes. Karyotyping analysis was performed. Whole exome sequencing was
performed to investigate the causative mutation.
Results: Whole exome sequencing revealed a novel splice site mutation in integrator complex
subunit 12 (INTS12) gene located on chromosome 4. This SNP (106,629,790 C>G) alteration
leads to an inclusion for 66 bp from the intron into the coding sequence resulting in a larger
polypeptide chain. 100 control cases were found negative for this INTS12 change.
Conclusion: Our results revealed an autosomal recessive association which affects many body
systems in the embryo in the early prenatal life. This association results in presence of a cluster
of congenital malformations. A splice site mutation in INTS12 that may affect the TGF-B1
pathway which is important in collagen expression and thus affect body tissue formation
Keywords: SALL1, SALL4, TOWNS BROCKS, VACTERAL association, INTS12, TGF-B
